Donor-specific B Cell Memory in Alloimmunized Kidney Transplant Recipients: First Clinical Application of a Novel Method

Wehmeier, Caroline and Karahan, Gonca E. and Krop, Juliette and de Vaal, Yvonne and Langerak-Langerak, Janneke and Binet, Isabelle and Schaub, Stefan and Roelen, Dave L. and Claas, Frans H.J. and Heidt, Sebastiaan and Swiss Transplant Cohort Study, . (2020) Donor-specific B Cell Memory in Alloimmunized Kidney Transplant Recipients: First Clinical Application of a Novel Method. Transplantation, 104 (5). pp. 1026-1032.

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Official URL: https://edoc.unibas.ch/76475/

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Background: HLA-specific memory B cells may contribute to the serum HLA antibody pool upon antigen re-exposure. The aim of this pilot study was to investigate the presence of concurrent donor-specific memory B cell-derived HLA antibodies (DSA-M) in renal allograft recipients with pre-transplant donor-specific HLA antibodies (DSA) and its association with occurrence of antibody-mediated rejection (ABMR) using a recently developed method. Methods: Twenty patients with Luminex single antigen bead (SAB) assay-defined DSA but negative complement-dependent cytotoxicity crossmatches were enrolled. Plasma samples and peripheral blood mononuclear cells (PBMC) were collected at 3 timepoints (pre-transplant, month 6, month 12). We analyzed IgG-purified and concentrated culture supernatants from polyclonally activated PBMC using SAB assays and compared HLA antibody profiles with same day plasma results. Results: Plasma SAB analysis revealed 35 DSA in 20 patients pre-transplant. DSA-M were detected in 9/20 (45%) patients and for 10/35 specificities (29%). While median mean fluorescence intensity (MFI) values of DSA with concurrent DSA-M (5877) were higher than those of DSA without DSA-M (1476), 3/6 patients with ABMR and low MFI DSA (<3000) had DSA-M. Overall, pre-transplant DSA/DSA-M pos allograft recipients showed a higher incidence of biopsy-proven (sub)clinical ABMR (p=0.032) and a higher extent (g≥1+ptc≥1) of microvascular inflammation (67% versus 9%, p=0.02). In 17 patients (28 DSA) with post-transplant analyses, persisting DSA post-transplant had more often DSA-M (6/12; 50%) than non-persisting DSA (2/16; 13%). Conclusion: Assessment of DSA-M might be a novel tool to supplement serum HLA antibody analysis for pre-transplant risk stratification in patients with DSA.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Nephrologie
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Nephrologie
UniBasel Contributors:Wehmeier, Caroline
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Wolters Kluwer
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:30 Sep 2020 01:30
Deposited On:24 Apr 2020 13:52

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